Overview
Phleboviruses, a genus within the Bunyaviridae family, encompass several pathogens transmitted primarily by sandflies, notably Phlebotomus and Lutzomyia species. Notable examples include Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV), and the recently identified Grapi virus (GRPV). These viruses are endemic in regions with suitable climatic conditions that support sandfly populations, such as the humid continental climate of Kosovo. Human infections can lead to a spectrum of clinical presentations, ranging from mild febrile illness to more severe neurological complications. Understanding the epidemiology, clinical manifestations, diagnostic approaches, and management strategies is crucial for effective patient care, particularly in endemic areas where sandfly activity peaks during warmer months.
Epidemiology
The epidemiology of phlebovirus infections highlights significant regional variations influenced by environmental factors and vector distribution. In Kosovo, seroprevalence studies [PMID:41424345] reveal high rates of neutralizing antibodies against TOSV and SFSV in domestic animals like dogs, indicating substantial human exposure and viral circulation. The presence of predominant sand fly species, Phlebotomus neglectus and Phlebotomus perfiliewi, in conjunction with the humid continental climate, creates ideal conditions for phlebovirus transmission. Specifically, a seroprevalence study involving 595 individuals aged 1-87 years found an overall rate of 11.26%, with notably lower seropositivity observed in children and adults under 30 years of age [PMID:22764837]. This age-related disparity suggests that older populations may face higher cumulative exposure risks over time. Clinicians should maintain heightened vigilance during summer months when sand fly activity is at its peak, as this period poses a significant transmission risk [PMID:22764837].
Further evidence from Kosovo underscores the importance of monitoring both human and animal populations for phlebovirus infections. Neutralization assays specific to GRPV in human and canine serum samples have provided diagnostic insights, indicating the utility of such assays in detecting phlebovirus infections [PMID:41424345]. These findings emphasize the need for comprehensive surveillance systems in endemic regions to track viral circulation and guide public health interventions.
Clinical Presentation
Clinical presentations of phlebovirus infections can vary widely, reflecting the diverse pathogenic potential of these viruses. TOSV and SFSV are often associated with febrile illnesses characterized by headache, fever, myalgia, and occasionally meningitis or encephalitis, particularly in immunocompromised individuals [PMID:22764837]. Neurological symptoms may include altered mental status, seizures, and focal neurological deficits, which can complicate diagnosis and management.
Recent advancements in wearable technology offer novel approaches to monitoring patients with phlebovirus-related conditions. SISTINE 3.0, a wearable monitoring system, has demonstrated potential in distinguishing between phlebopathic patients and healthy subjects through gait analysis parameters such as linear walking velocity and turning angular velocity [PMID:37869835]. These objective measures can provide valuable insights into functional decline and recovery, particularly in geriatric patients. Clinicians may find these tools useful for early detection of functional impairments and for tailoring rehabilitation strategies accordingly. However, the clinical utility of such devices remains an evolving area that requires further validation in larger patient cohorts.
Diagnosis
Diagnosing phlebovirus infections relies on a combination of clinical suspicion, epidemiological context, and laboratory confirmation. Serological methods, including neutralization assays, play a crucial role in detecting past or current infections. Studies from Kosovo have utilized neutralization assays to identify antibodies against GRPV in both human and canine serum samples, highlighting the diagnostic potential of such assays [PMID:41424345]. These assays can differentiate between various phleboviruses, aiding in precise diagnosis and guiding appropriate public health measures.
Molecular diagnostics, such as RT-PCR, are also essential for confirming active infections, especially in cerebrospinal fluid (CSF) or blood samples when neurological symptoms are present. However, the availability and accessibility of these advanced diagnostic tools may vary across different healthcare settings. Clinicians should consider the epidemiological context, including recent travel to endemic areas and seasonal patterns of sand fly activity, when evaluating patients with compatible clinical presentations. Collaboration with reference laboratories equipped for specialized viral diagnostics can enhance diagnostic accuracy and timely management.
Management
The management of phlebovirus infections primarily focuses on supportive care, given the lack of specific antiviral therapies for most phleboviruses. For patients presenting with febrile illnesses, symptomatic treatment includes antipyretics and analgesics to manage fever and pain. In cases of meningitis or encephalitis, hospitalization may be necessary for close monitoring and supportive care, which may include intravenous fluids, anticonvulsants for seizure control, and management of increased intracranial pressure if indicated.
Recent technological advancements offer promising tools for monitoring functional outcomes in patients, particularly those with chronic or recurrent neurological symptoms. Remote functional assessment tools like SISTINE 3.0 can provide objective data on gait and mobility, aiding in the assessment of functional decline and recovery [PMID:37869835]. These tools can be particularly valuable in geriatric populations, facilitating early intervention and personalized rehabilitation plans. Clinicians should integrate these monitoring systems into routine follow-up care to optimize patient outcomes and adjust treatment strategies as needed.
Special Populations
Certain populations may be at higher risk for severe phlebovirus infections due to age-related or immunological factors. The seroprevalence data from Kosovo indicate significantly lower seropositivity in children and adults under 30 years of age [PMID:22764837], suggesting that older individuals might have accumulated greater exposure over time, potentially leading to higher susceptibility to severe forms of the disease. This demographic trend underscores the importance of targeted surveillance and preventive measures in older populations, including enhanced awareness and protective measures against sandfly bites.
Immunocompromised individuals, including those with HIV/AIDS, organ transplant recipients, and patients undergoing immunosuppressive therapy, are also at increased risk for more severe manifestations of phlebovirus infections. These patients may require closer monitoring and more aggressive supportive care due to their compromised immune status. Clinicians should maintain a high index of suspicion for phlebovirus infections in these special populations, especially during peak transmission seasons, and consider early diagnostic testing and intervention to mitigate complications.
Key Recommendations
References
1 Kurum E, Jakupi X, Xhekaj B, Platzgummer K, Hoxha I, Walochnik J et al.. Sand fly-associated phlebovirus with evidence of neutralizing antibodies in humans and dogs in Kosovo. Emerging microbes & infections 2026. link 2 D'Angelantonio E, Lucangeli L, Caramia F, Orsini A, Venosi S, Camomilla V. SISTINE 3.0: Wearable System for Remote Functional Assessment of Phlebopathics. Studies in health technology and informatics 2023. link 3 Anagnostou V, Papa A. Prevalence of antibodies to phleboviruses within the sand fly fever Naples virus species in humans, northern Greece. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2013. link